ROLE OF CD44 IN THE DEVELOPMENT OF NATURAL-KILLER-CELLS FROM PRECURSORS IN LONG-TERM CULTURES OF MOUSE BONE-MARROW

The role of the adhesion molecule CD44 in the development of NK cells was analyzed in a mouse long-term bone marrow culture system. After 4 wk of culture (day 0), recombinant human IL-2 was added and 13 days la ter the cells generated were shown to have substantial cytotoxic activ ity against YAC-1 and to be enriched for NK cells, as assessed for NK- 1.1 phenotype by flow cytometric analysis. Physical separation between stroma and precursors partially inhibited proliferation and, conseque ntly, a lower number of cytotoxic cells were produced. Similar results were obtained when an anti-CD44 mAb was added together with IL-2 at d ay 0. The disruption of hyaluronic acid (HA), one of the ligands of CD 44, by hyaluronidase or the competition for the binding of CD44 by sol uble HA added with IL-2 on day 0 inhibited both proliferation and deve lopment of cytotoxicity to a greater degree than did anti-CD44. These results indicate that interaction of CD44 with HA plays an important r ole in the development of pre-NK cells into cytotoxic effector cells.